Method and apparatus for limiting growth of eye length

ABSTRACT

Certain embodiments of the present invention are directed to therapeutic intervention in patients with eye-length-related disorders to prevent, ameliorate, or reverse the effects of the eye-length-related disorders. Embodiments of the present invention include methods for early recognition of patients with eye-length-related disorders, therapeutic methods for inhibiting further degradation of vision in patients with eye-length-eye-length-related disorders, reversing, when possible, eye-length-related disorders, and preventing eye-length-related disorders. Additional embodiments of the present invention are directed to particular devices used in therapeutic intervention in patients with eye-length-related disorders.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit the Provisional Application No.61/139,938, filed Dec. 22, 2008.

GOVERNMENT STATEMENT OF RIGHTS

The government has certain rights to the application under federallysponsored research through the National Institutes of Health (NIH) GrantNo. EY009620LD.

TECHNICAL HELD

The present invention is related to treatment of eye-length-relateddisorders, including myopia, to various therapeutic devices employed totreat patients with eye-length-related disorders, and to various methodsand devices for generally controlling eye growth in biologicalorganisms.

BACKGROUND OF THE INVENTION

The eye is a remarkably complex and elegant optical sensor in whichlight from external sources is focused, by a lens, onto the surface ofthe retina, an array of wavelength-dependent photosensors. As with anlens-based optical device, each of the various shapes that the eye lenscan adopt is associated with a focal length at which external light raysare optimally or near-optimally focused to produce inverted images onthe surface of the retina that correspond to external images observed bythe eye. The eye lens, in each of the various shapes that the eye lenscan adopt, optimally or near-optimally, focuses light emitted by, orreflected from external objects that lie within a certain range ofdistances from the eye, and less optimally focuses, or fails to focusobjects that lie outside that range of distances.

In normal individuals, the axial length of the eye, or distance from thelens to the surface of the retina, corresponds to a focal length fornear-optimal focusing of distant objects. The eyes of normal individualsfocus distant objects without nervous input to muscles which applyforces to alter the shape of the eye lens, a process referred to as“accommodation.” Closer, nearby objects are focused, by normalindividuals, as a result of accommodation. Many people suffer fromeye-length-related disorders, such as myopia, in which the axial lengthof the eye is longer than the axial length required to focus distantobjects without accommodation. Myopic individuals view closer objectswithin a range of distances less than typical distant objects, withoutaccommodation, the particular range of distances depending on the axiallength of their eyes, the shape of their eyes, overall dimensions oftheir eyes, and other factors. Myopic patients see distant objects withvarying degrees of blurriness, again depending on the axial length oftheir eyes and other factors. While myopic patients are generallycapable of accommodation, the average distance at which myopicindividuals can focus objects is shorter than that for normalindividuals. In addition to myopic individuals, there are hyperopicindividuals who need to accommodate, or change the shape of theirlenses, in order to focus distant objects.

In general, babies are hyperopic, with eye lengths shorter than neededfor optimal or near-optimal focusing of distant objects withoutaccommodation. During normal development of the eye, referred to as“emmetropization,” the axial length of the eye, relative to otherdimensions of the eye, increases up to a length that providesnear-optimal focusing of distant objects without accommodation. Innormal individuals, biological processes maintain the near-optimalrelative eye length to eye size as the eye grows to final, adult size.However, in myopic individuals, the relative axial length of the eye tooverall eye size continues to increase during development, past a lengththat provides near-optimal focusing of distant objects, leading toincreasingly pronounced myopia.

The rate of incidence of myopia is increasing at alarming rates in manyregions of the world. Until recently, excessive reading during childhoodwas believed to be the only identifiable environmental or behavioralfactor linked to the occurrence of myopia, although genetic factors weresuspected. Limiting reading is the only practical technique forpreventing excessive eye lengthening in children, and corrective lenses,including glasses and contact lenses, represent the primary means forameliorating eye-length-related disorders, including myopia. The medicalcommunity and people with eye-length-related disorders continue to seekbetter understanding of eye-length-related disorders and methods forpreventing, ameliorating, or reversing eye-length-related disorders.

SUMMARY OF THE INVENTION

Certain embodiments of the present invention are directed to therapeuticintervention in patients with eye-length-related disorders to prevent,ameliorate, or reverse the effects of the eye-length-related disorders.These embodiments of the present invention include methods for earlyrecognition of patients with eye-length-related disorders, therapeuticmethods for inhibiting further degradation of vision in patients witheye-length-related disorders, reversing, when possible,eye-length-related disorders, and preventing eye-length-relateddisorders. Additional embodiments of the present invention are directedto particular devices used in therapeutic intervention in patients witheye-length-related disorders.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a cross-section view of a human eye.

FIG. 2 illustrates the optical-sensing structures within the retina ofthe eye.

FIG. 3 illustrates the interconnection of photoreceptor neural cellsthrough higher layers of neural circuitry.

FIG. 4 illustrates an opsin photoreceptor protein.

FIG. 5 schematically illustrates biological photoreception and lowerlevels of biological image processing.

FIG. 6 provides a top-down view of the patch of photoreceptor neuronsshown in FIG. 5.

FIGS. 7A-B illustrate an example of w-level neural processing ofphotoreceptor neural cell signals.

FIG. 8A illustrates a plot of the spatial frequency of images input tothe retina versus axial length of the eye, when relatively distantscenes are observed.

FIG. 8B shows an image of a distant scene, as input to the retina,corresponding to different axial lengths of the eye.

FIGS. 9A-C illustrate, using state-transition diagrams, control of eyelengthening in normal developing humans, lack of control of eyelengthening in myopic humans, and a therapeutic approach of certainembodiments of the present invention used to prevent, ameliorate, orreverse various types of eye-length-related disorders.

FIG. 10 provides a control-flow diagram that describes a generalizedtherapeutic invention that represents one embodiment of the presentinvention.

FIG. 11 illustrates an exemplary therapeutic device that is used toprevent ameliorate, or even reverse myopia induced by excessive reading,and/or other behavioral, environmental, or genetic factors, and thatrepresents one embodiment of the present invention.

FIG. 12 illustrates axial-length versus age curves for normalindividuals, myopic individuals, and myopic individuals to whichtherapeutic interventions that represent embodiments of the presentinvention are applied.

FIG. 13 illustrates experimental results that confirm the effectivenessof the therapeutic device and therapeutic intervention that arediscussed with reference to FIGS. 10 and 11 and that representembodiments of the present invention.

FIGS. 14A-15 illustrate the source of hypervariability thatcharacterizes the genes that encode the L and M opsins.

FIG. 16 illustrates the effects of genetic variation in opsin genes onthe absorbance characteristics of the opsin photoreceptor protein.

FIG. 17 illustrates the effects on average spatial frequency of imagesinput to the retina produced by certain types ofopsin-photoreceptor-protein variants.

FIG. 18 illustrates the predictability of the degree of myopia inindividuals with various types of mutant opsin photoreceptor proteins,according to one embodiment of the present invention.

FIGS. 19A-B illustrate characteristics of the filters employed in thetherapeutic devices used to treat variant-photoreceptor-protein-inducedmyopia as well as myopia induced by other, or combinations of other,environmental, behavioral, or genetic factors, according to certainembodiments of the present invention.

FIGS. 20A-I illustrate, using exemplary ƒ(x) and g(x) functions, theconvolution operation, ƒ(x)·g(x), of two functions ƒ(x) and g(x).

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 provides a cross-section view of a human eye. The eye 102 isroughly spherical in shape, and is encased by a tough, white outer layer104, referred to as the “sclera,” and a transparent cornea 106 throughwhich light from external light sources passes to enter the pupil 108.Light passing through the pupil is focused by the lens 110 onto thesemi-spherical retina 112 that forms a large portion of the internalsurface of the solution-filled 114 sphere of the eye. The retinaincludes photoreceptor neurons hierarchically interconnected throughhigher-level neuronal structures that ultimately connect tophotoreceptor neurons the optical nerve 116, through which optical datacollected by the retina and processed by the higher-level neuronalstructures are passed to the central nervous system. The iris 118operates as a shutter to vary the diameter of the pupil, and thus varythe light flux entering the pupil. The process of accommodation, inwhich the shape of the eye lens is changed to focus objects at variousdistances onto the retina, involves nervous excitation of the ciliarymuscles 120.

FIG. 2 illustrates the optical-sensing structures within the retina ofthe eye. In FIG. 2, a small portion 202 of the retina is shown, incross-section at higher magnification 204. Photoreceptor neurons, suchas photoreceptor neuron 206, form a relatively dense outer layer of theretina along the cells of an inner layer of the eye 208. Thephotoreceptor neural cells, such as photoreceptor neuron 206, interface,through neural synapses, to bipolar cells, such as bipolar cell 210,which in turn interface to horizontal neural cells 212 and higher layersof neural cells that eventually interconnect the photoreceptor neuronswith the optic nerve 214. The photoreceptor neurons are thephoton-sensing elements of the retina, transducing impinging photonsinto neural signals communicated to the bipolar cells 210 via synapses,such as synapse 216.

FIG. 3 illustrates the interconnection of photoreceptor neural cellsthough higher layers or neural circuitry. In FIG. 3, a dense forest ofphotoreceptor neurons, including as photoreceptor neuron 302, forms aportion of the outer retina layer of the eye. The photoreceptor neuronsare interconnected through bipolar, horizontal, and higher-level neuralcells, represented, in the aggregate, by the neural interconnectionlayer 304. The higher-level interconnection level 304 provides initiallayers of neural processing of raw photoreceptor signals. Each differenttype of photoreceptor neuron contains a corresponding type ofphotoreceptor protein, including rhodopsin for rod photoreceptor neuronsand one of three different types of opsin photoreceptor proteins in thecase of three different, corresponding types of cone photoreceptorneurons. Photoreceptor proteins conformationally respond to aconformation change of a retinal co-factor pigment molecule, from a cisto trans conformation, that results from absorption, by the co-factor,of a photon of light having an energy within an energy range to whichthe opsin photoreceptor protein is responsive. Conformation change ofthe photoreceptor protein alters interaction of the photoreceptorprotein with an adjacent transducer protein, activating the transducerto, in turn, activate a cyclic-guanosine-monophosphate (“cGMP”) specificphosphodiesterase. The cGMP-specific phosphodiesterase hydrolyzes cGMP,reducing the intracellular concentration of cGMP which, in turn, causesgated ion channels in the photoreceptor-neuron membrane to close.Closing of the gated ion channels results in hyperpolarization of thephotoreceptor-neuron membrane, which, in turn, alters the rate ofrelease of the neurotransmitter glutamate into the synapse connectingthe photoreceptor neuron with higher layers of retinal neural circuitry.In essence, at some threshold-level change in glutamate release, thebipolar cell emits a electrochemical signal into the higher levels ofretinal neural circuitry. However, the retinal neural circuitry does notsimply aggregate individual photoreceptor-neural-cell-initiated signals,but instead carries out initial levels of neural processing, includingfeedback inhibition of photoreceptor-neural cells based on the spatialand temporal states of neighboring photoreceptor neurons and manylower-level image-processing tasks analogous to the lower-levelimage-processing tasks carried out by various computationalimage-processing systems, including edge detection, feature detectioncontrast modulation, and other such tasks.

FIG. 4 illustrates an opsin photoreceptor protein. Opsins are members ofthe transmembrane protein family, in particular, the membrane-boundprotein-coupled receptors. In FIG. 4, the opsin photoreceptor protein isillustrated as a string of beads 402, each bead representing anamino-acid monomer. The cylindrical features in the illustration, suchas cylindrical feature 404, represent transmembrane alpha helicalsegments that span the photoreceptor-neuron membrane. As mentionedabove, there are three different types of opsins, referred to below as Sopsin, M opsin, and L opsin. The M and L opsins are homologous, having98-percent amino-acid-sequence identity. In primordial L and M opsins,the amino-acid monomers at 11 positions within the amino acid sequenceof the opsins, labeled in FIG. 4 by sequence number, are different. Asdiscussed in greater detail, below, the genes encoding the M and Lopsins are hypervariable. As a result, there are many differentvariants, in modern humans, of both the L and M opsin photoreceptorproteins, with much of the variation involving the 11 amino acidslabeled by sequence number in FIG. 4.

FIG. 5 schematically illustrates certain aspects of the biology ofbiological photoreception and lower levels of biological imageprocessing. In FIG. 5, a small patch, or rectangular area 502 of thephotoreceptors at the outer portion of a human retina is shownschematically. The retina, of course, contains huge numbers ofphotoreceptor neurons. The photoreceptor neurons, such as photoreceptorneuron 504, are shown as ellipsoids, with the outmost end of theellipsoids shading-coded to indicate the type of photoreceptor neuron.Only cone photoreceptor neurons are shown in FIG. 5. The retina alsoincludes a large number of rod photoreceptor neurons. The photoreceptorneurons are connected, at the opposite end, to the higher-level neuralcircuitry 506 represented as a rectangular substrate, or array, fromwhich a final optical signal 508 emerges. The structure schematicallyshown in FIG. 5 bears similarity to many electronic optical-receptordevices. In FIG. 5, three graphs 510-512 show the absorbance spectra forthe three different types of photoreceptor neurons. In each graph, thevertical axis, such as vertical axis 516 in graph 510, representsnormalized absorbance values. The absorbance at wavelength λ, a formallyunitless quantity, is defined as

${A_{\lambda} = {- {\ln \left( \frac{I}{I_{0}} \right)}}},$

where I is the intensity of light of wavelength λ that has passedthrough a sample, and I₀ is the intensity of the incident light ofwavelength λ. The horizontal axes, such as horizontal axis 518 in graph510, represent the wavelength of the incident light. Graph 510 shows theabsorbance spectrum for the S opsin, which features a maximum absorbance520 for light of wavelength λ=420 mm. The S of “S opsin” stands forshort-wavelength. Note that the shading-coding 524 for S photoreceptorneurons, which contain S opsin, is shown to the right of the graph.Graph 511 shows the absorbance spectrum for the M, or medium-wavelength,photoreceptor neuron, and graph 512 shows the absorbance spectrum forthe L, or long-wavelength, photoreceptor neuron. The different types ofopsin molecules in each of the three different types of photoreceptorneurons determine the different absorption characteristics of the threedifferent types of photoreceptor neurons. The difference absorptioncharacteristics of the three different types of photoreceptor neuronsprovides the three dimensions of human color vision.

FIG. 6 provides a top-down view of the patch of photoreceptor neuronsshown in FIG. 5. Viewed top-down, the photoreceptor neurons appear asshading-coded disks. The shading coding is the same shading coding usedin FIG. 5. As shown in FIG. 6, the L and M photoreceptor neuronstogether comprise roughly 95 percent of the total number ofphotoreceptor neurons. As illustrated in FIG. 6, the distribution of thedifferent types of photoreceptor neurons appears somewhat disordered,but is not random.

FIGS. 7A-B illustrate an example of low-level neural processing ofphotoreceptor neuron signals. For purposes of illustrating this exampleof low-level neural processing, the types of the photoreceptor neuronsare irrelevant, and not shown in FIGS. 7A-B by shading coding. FIGS.7A-B show the same patch or area of photoreceptor neurons that is shownin FIG. 6. In FIG. 7A, a sharp illumination edge falls across the patchof photoreceptor neurons. The more highly illuminated photoreceptorneurons 702 are shown without shading, and the less-illuminatedphotoreceptor neurons are shaded 704. Line 706 represents the boundarybetween more highly illuminated and less illuminated photoreceptorneurons. Such boundaries, or edges, frequently occur in images, such asthe outline of a building against the sky or edge of a printed characteron a white page. In FIG. 7B, the signal responses of the photoreceptorneurons is indicated by shading with the cells emitting highest-levelresponses shaded darkly and photoreceptor neurons emitting lowest-levelresponses unshaded. As can be seen in FIG. 7, the photoreceptor neuronsthat respond most actively to the input illumination lie adjacent to thedark-light boundary 706. The lower-illuminated photoreceptor neuronsdistant from the boundary exhibit low signal response, such aslower-illuminated photoreceptor neuron 708, while the illuminatedphotoreceptor neurons distant from the dark-light boundary, such asphotoreceptor neuron 710, exhibit only slightly higher signal responsethan the lower-illuminated photoreceptor neurons distant from thedark-light boundary, but substantially lower signal response than thecells lying along the dark-light edge. This type of signal response isachieved, in the layers of neural circuitry, (506 in FIG. 5), vianegative feedback of photoreceptor neurons by similarly responding, orsimilarly illuminated, neighboring photoreceptor neurons. By contrast,photoreceptor neurons with neighboring photoreceptor neurons showingsignificantly different signal responses, such as the photoreceptorneurons near the dark-light edge (706 in FIG. 7B), receive positivefeedback, boosting their signal response. This is similar tocomputational edge detection, in which a Laplacian operator or otherdifferential operator is convolved with pixels of an image in order toheighten pixel values for pixels near or along edges and lower the pixelvalues for pixels within regions of relatively constant pixel value, orlow contrast. Clearly, the aggregate signal response from thephotoreceptor neurons in an area of photoreceptor neurons within theretina is proportional to the spatial frequency, or granularity ofcontrast, of an image focused onto the area of the retina by the lens ofthe eye. In general, a focused image of a distant scene input to theretina produces significantly higher spatial frequency, or edginess,than input of a blurry, or out-of-focus image. Thus, the higher-levelneural circuitry within the retina of the eye can directly detect andrespond to spatial frequency, or edginess, of an image input to theretina and can therefore indirectly detect and respond to the degree towhich images are focused.

The present inventors, through significant research efforts, haveelucidated the mechanism by which the axial length of the eye iscontrolled during development. FIG. 8A illustrates a plot of the spatialfrequency of images input to the retina versus axial length of the eye,when relatively distant scenes are observed. FIG. 8B shows an image of adistant scene, as input to the retina, corresponding to different axiallengths of the eye. As shown in FIG. 8A, the curve of the spatialfrequency versus axial length exhibits an inflection point at between 22and 24 mm 804, with the spatial frequency rapidly decreasing between eyeaxial lengths of 21 mm and 24 mm. As shown in FIG. 8B, a bamboo plantappears sharply focused on the retina 810 at an axial length of 16 mm812 but becomes noticeably blurry 814 at an axial length of 24.5 mm 816.As discussed above, the blurriness of the image can be directly detectedand responded to by the lower layers of neural circuitry within theretina. It turns out that the axial length of the eye is controlled,during development, by a positive eye-lengthening signal, a negativefeedback signal, or both a positive eye-lengthening signal and anegative feedback signal produced by the neural circuitry within theretina. A positive eye-lengthening signal is turned off in response tothe average spatial frequency of images input to the retina decreasingbelow a threshold spatial frequency, while a negative feedback signal isturned on in response to the average spatial frequency of images inputto the retina decreasing below a threshold spatial frequency. Asmentioned above, babies are generally hyperopic. In the hyperopic state,a positive eye-lengthening signal ma be produced by the retinal neuralcircuitry to lengthen the eye towards the proper length for focusingdistant objects. As the eye lengthens past a point at which distantobject lose focus, and threshold spatial frequency decreases below thethreshold value, around 24.5 mm for developing eyes in preadolescentchildren, the positive eye-lengthening signal is turned off, so that theeye does not further lengthen and further blur distant images.Alternatively, the shutdown of eye lengthening may occur as a result ofa negative feedback signal that is initiated by decrease in averagespatial frequency of images, input to the retina, past a thresholdspatial frequency.

FIGS. 9A-C illustrate, using state-transition diagrams, control of eyelengthening in normal developing humans, lack of control of eyelengthening in myopic humans, and a therapeutic approach of certainembodiments of the present invention used to prevent, ameliorate, orreverse various types of eye-length-related disorders. Of course, inbiological systems, the assignment of conceptual states to biologicalstates is arbitrary, and used to emphasize certain aspects of thebiological state. For example, there may be many ways to assign a widevariety of different states to any particular biological system. Thestate transition diagrams are used to illustrate the dynamics of certainaspects of systems, rather than provide a full, detailed description ofthe systems. Note that, in FIGS. 9A-C, a positive eye-lengthening signalis assumed. Similar transition-state diagrams are readily developed fora negative feedback signal that prevents further eye lengthening. FIG.9A provides a state-transition diagram representing normal control ofeye lengthening during development. In an initial state 902, into whichthe vast majority of humans are born, the spatial frequency of imagesinput to the retina is generally high, and the images are either infocus, without accommodation, or focus can be achieved by accommodation.The eye can transition from the first state 902 to a second state 904,in which there is, on average, less spatial frequency in images input tothe retina and the images are very slightly out of focus. The eyetransitions from state 902 to 904 as a result of an eye-lengtheningsignal, represented by edge 906, produced by the higher levels of neuralcircuitry within the retina. The eye can transition to a third state908, as a result of additional eye-lengthening signals 910, in whichthere is, on average, less than a threshold amount of spatial frequencyin images input to the retina, and the input images are, for distantscenes and objects, out of focus. Once the threshold spatial frequencyhas been crossed, the eye no longer receives, or responds to, theeye-lengthening signal. This can be seen in FIG. 9A by the absence ofeye-lengthening-signal arcs emanating from state 908. The eye cannotlengthen further once the eye resides in the third state 908. However,as the eye continues to develop and grow, the eye can transition fromthe third state 908 back to the second state 904. During development,the eye intermittently transitions between the second state 904 andthird state 908 so that the axial length of the eye grows at a ratecompatible with the overall growth of the eye and development-inducedchanges in other eye characteristics. Ultimately, in late adolescence orearly adulthood, the eye no longer responds to the eye-lengtheningsignal, the eye no longer continues to grow and develop, and the eyetherefore ends up stably residing in either the third state 908.

As shown in the graph 920, in the lower portion of FIG. 9A, in which therate of eye growth, plotted with respect to the vertical axis, dependson the spatial frequency or blurriness, of images input to the retina,plotted with respect to the horizontal axis, eye growth continues at ahigh rate 922 up until a threshold spatial frequency 924 is reached,after which eye growth falls rapidly, at least temporarily fixing theaxial length of the eye to an axial length at which the averageblurriness of images input to the retina is slightly greater than theblurriness threshold that triggered inhibition of the eye-lengtheningsignal.

FIG. 9B illustrates a state-transition diagram for myopic individualsand individuals suffering from other eye-length-related disorders, usingthe same illustration conventions as used for FIG. 9A. In this case, thefirst two states 930 and 932 are identical to the first two states (902and 904 in FIG. 9) shown in FIG. 9A. However, a new third state 934represents a state in which the average spatial frequency of imagesinput to the retina is decreased from the level of spatial frequency ofstate 932, but still greater than the threshold spatial frequency thattriggers inactivation of the eye-lengthening signal and/or activation ofa negative-feedback signal to stop eye lengthening. In this third state,unlike the third state (908 in FIG. 9A) of the normal state-transitiondiagram, the eye remains responsive to the eye-lengthening signal 936and continues to grow. This third state may result from environmentalfactors, behavioral factors, genetic factors, additional factors orcombinations of various types of factors. Note that the final state, inwhich the average spatial frequency of input images falls below athreshold spatial frequency, and from which the eye can no longerlengthen 940, is not connected to the other states by arcs, and istherefore unreachable from the other states. As shown in graph 942 inthe lower portion of FIG. 9B, eye growth continues, at a high rate,beyond the threshold spatial frequency that normally triggers cessationof eye lengthening.

FIG. 9C illustrates an approach to preventing excessive eye lengtheningthat underlies therapeutic embodiments of the present invention. FIG. 9Cincludes the same states 930, 932, 934, and 940 that appear in thestate-transition diagram of FIG. 9B. However, unlike in thestate-transition diagram shown in FIG. 9B, the state-transition diagramshown in FIG. 9C includes an additional edge or arc 950 that provides atransition from the third state 934 to state 940, in which the eye canno longer lengthen. Any therapy or therapeutic device that can decreasethe average spatial frequency of images input to the retina, indicatedby arrow 950, forces a state transition to the final state 940 that isidentical to state 908 in FIG. 9A, in which the eye can no longerlengthen, and represents an embodiment of the present invention. Theseembodiments of the present invention may include specialized glasses,contact lenses, and other devices, drug therapies, behavior-modificationregimes, and other such devices and therapeutic techniques. In general,this transition 950 can be described as a method for introducingartificial blurring of the images input to the eye retina, so that theaverage spatial frequency of the images falls below the thresholdspatial-frequency value that triggers inhibition of continued eyelengthening. Of course, when artificial blurring is discontinued, asrepresented by arrow 952, the eye transitions back to state 934. As withstate 908 in FIG. 9A, the eye can also transition from state 940 back toeither of states 932 or 934 when the characteristics of the eye changethrough development, rendering an applied artificial blurringinsufficient to maintain the eye in state 940, or when artificialblurring is no longer applied. As shown in graph 960 at the bottom ofFIG. 9C, when an eye lengthening-related disorder can be recognized ordiagnosed, prior to transition of the eye to state 934, then artificialblurring can be applied to force cessation of eye lengthening at a pointidentical to, or similar to, the point when, in normal development, adecrease in spatial frequency past the threshold spatial frequencyinhibits further eye lengthening as represented by curve 962. Thisrepresents application of a therapeutic intervention that preventseye-lengthening-related disorders. However, even when the eye has grownpast its proper axial length, represented by curve 964, application ofartificial-blurting-based therapies can nonetheless ameliorate theeffects of the eye-length-related disorder. As discussed further, below,this amelioration can transform, in certain cases, into a reversal ofthe eye-length-related disorder as the eye continues to develop duringchildhood.

FIG. 10 provides a control-flow diagram that describes a generalizedtherapeutic invention that represents one embodiment of the presentinvention. In step 1002, information is received for a patient. In step1004, a determination is made as to whether the patient has aneye-length-related disorder. This determination can be made in a varietyof different ways. For example, certain vision tests may reveal nascentmyopia in preadolescent or adolescent children. Alternatively, variousinstruments can be used to directly measure the axial length of the eye,and compare the measured axial length or the ratio of the measured axiallength to other eye characteristics to a standard axial length or ratiofor similarly aged or sized individuals. If a disorder is present, asdetermined in step 1006, then the therapeutic intervention representedby the while-loop of steps 1008-1012 continues until the eye no longerresponds to an eye-lengthening signal or until the eye-length-relateddisorder is no longer present. During each iteration of the while-loop adetermination is made, in step 1009 of the discrepancy between thecurrent eye length and an appropriate eye length for the particularpatient. Then, in step 1010, a device or process is applied to thepatient to induce a level of artificial blurring commensurate with thediscrepancy determined in step 1009. The level of applied artificialblurring may be proportional to the discrepancy determined in step 1009inversely related to the discrepancy determined in step 1009, orconstant over a range of discrepancies, depending on the current stageof the eye-length-related disorder, on the type of eye-length-relateddisorder, and on other factors. After a period of time represented bystep 1011, when eye lengthening is still a potential problem controlreturns to step 1009 to again evaluate the patient for additionalapplication of artificial blurring.

As mentioned above, excessive reading by children is one cause ofmyopia. The human eye evolved for observing relatively distant scenesand objects, rather than for focusing on detailed, close-by objects,such as printed text. Continuous close focusing on printed text resultsin relatively high spatial frequency images input to the retina,overriding the blurriness introduced in distant scenes and objects dueto eye lengthening. FIG. 11 illustrates an exemplary therapeutic devicethat is used to prevent, ameliorate, or even reverse myopia induced byexcessive reading, and or other behavioral, environmental, or geneticfactors, and that represents one embodiment of the present invention.This device comprises a pair of glasses 1102 into the lenses of whichsmall bumps or depressions, translucent inclusions or transparentinclusions with a refractive index different from that of the lensmaterial, or other such features, represented in FIG. 11 by small blackdots across the lenses of the glasses, are introduced in order to blurimages observed by a patient wearing the glasses. One lens includes aclear area 1104 to allow sharp focus, so that the glasses wearer cancontinue to read and undertake other normal activities. A complementarypair of glasses 1106 features a clear area 1108 in the opposite lens. Byalternating wearing of each of the pair of glasses, artificial blurringis introduced to force the average spatial frequency of images input tothe retina of the glasses wearer below the spatial-frequency threshold,at which further eye lengthening is at least temporarily prevented. InFIG. 11, each of the two pairs of glasses is indicated as being worn onalternate weeks, but in other embodiments of the present invention, theperiods during which each of the two pairs of glasses are worn maydiffer from a period of one week, as indicated in FIG. 11, and maydiffer from one another, as well. In FIG. 11, the plots ofdots-per-square-millimeter vs. distance from an edge of the lens, 1110and 1111, illustrate the radial distribution of dot density from thecenter of the lenses. Decreasing dot density in the central region ofthe lenses facilitates relatively normal image acquisition for portionsof scenes axially aligned with the axis of the eye, which are generallythe portions of scenes that an observer is concentrating his vision onwhile increasingly blurring the portions of scenes that are not alignedwith the optical axis. The amount of artificial blurring produced by thetherapeutic device can be controlled, by varying dot densities, dotdimensions, the material of inclusions, or by varying additional ormultiple characteristics of the therapeutic device, to reduce visualacuity from 20/20 to acuity in the range of about 25/20, in certainembodiments of the present invention.

In another embodiment of the present invention, artificial blurring isproduced by light scattering induced by incorporation of particlessmaller than the wavelength of the light transmitted through the lensesor produced by a film or coating applied to the surface of the lens. Theamount of scatter produced by different regions of the lens can bevaried to closely mimic the blur produced in a typical scene viewedthrough a near-accommodated emmetropic eye.

In yet another embodiment of the present invention, diffraction is usedto provide the blurring. Opaque or semi-opaque light absorbing particlesas large or larger than the wavelength of light transmitted through thetherapeutic-device lenses are incorporated into the lenses, applied tothe surface of the lenses, or added as a film or coating. In vet anotherembodiment of the present invention, diffusers can be used to impartblurring to the lens.

In alternative embodiments of the present invention, various types ofprogressive lenses are employed to introduce artificial blurring.Currently-available progressive lenses work to provide the most stronglynegative correction in the upper part of the lens and provide a lessnegative correction at the bottom of the lens. These correctionsfacilitate focusing the visual field both for distant and up-closeobjects. An inverse progressive lens that provides a least negativecorrection at the top and a most negative correction at the bottom wouldprovide an artificial blur over the entire visual field, and would thusconstitute an additional embodiment of the present invention. Glasses orcontact lenses that introduce blur by including higher-order aberration,including glasses or contact lenses that produce peripheral aberrations,leaving the center of vision in focus, represent still additionalembodiments of the present invention.

FIG. 12 illustrates axial-length versus age curves for normalindividuals, myopic individuals, and myopic individuals to whichtherapeutic interventions that represent embodiments of the presentinvention are applied. A normal individual, represented by curse 1202,shows a constant lengthening of the eye up to late adolescence or earlyadulthood, at which point eye length remains fixed at a length ofgenerally between 24 and 25 mm. The constant rate is controlled, asdiscussed above, by frequent transitions of the eye between states 932and 934 in FIG. 9B. By contrast, in myopic individuals, represented inFIG. 12 by curve 1204, eye growth occurs at a much greater rate,represented by the greater slope of the linear portion of curve 1204with respect to the curve for normal individuals 1202. As discussedabove, this greater rate of eye lengthening corresponds to the eyeremaining in state 934, in FIG. 9B, in which the eye remains responsiveto an eye-lengthening signal, or unresponsive to a negative-feedbacksignal, due to excessive reading or other environmental or geneticfactors. As shown by curve 1206, application of artificial blurring atfive years of age increases the rate of eye lengthening and caneventually force eye length to a length slightly above, or at the eyelength of normal individuals. Curve 1206 thus represents a case in whichthe effects of an eye-length-relating disorder are reversed bytherapeutic intervention.

FIG. 13 illustrates experimental results that confirm the effectivenessof the therapeutic device and therapeutic intervention that arediscussed with reference to FIGS. 10 and 11 and that representembodiments of the present invention. This is data was obtained for 20eyes from children, all between the ages of 11 and 16, who haveprogressing myopia and all of whom have opsin mutations that contributeto the progression of myopia. The results show that that therapeuticinter brings the axial length growth rate into the normal range,preventing myopia. As shown in the graph 1302, the rate of eyelengthening represented by curve 1304, decreases significantly inindividuals employing the therapeutic device illustrated in FIG. 11 incontrast to individuals wearing normal, control lenses, represented bycurve 1306. Graph 1310 shows the growth rate of axial length, inmicrometers per day for individuals wearing the therapeutic device shownin FIG. 11 1310 versus the growth rate for individuals wearing thecontrol lens 1312.

FIGS. 14A-15 illustrate the source of hypervariability thatcharacterizes the genes that encode the L and M opsins. As shownschematically in FIG. 14A, the genes that encode the L and M opsins arelocated near one another, towards the end of the X chromosome 1402. InFIG. 14A, and in FIGS. 14B-D below, the two anti-parallel strands of DNAthat together represent the X chromosome are shown one above the other,with arrows 1404 and 1406 indicating the polarity of each DNA strand.FIG. 14B illustrates the process of meiosis, in which a cell undergoestwo divisions to produce four haploid gamete cells. The process is shownonly with respect to the terminal portion of the X chromosome. Theillustrated process occurs only in females, with respect to the Xchromosome. In females, each of the two different X chromosomes 1410 and1412 are replicated to produce a second copy of each chromosome1414-1416, respectively. During the first cell division, the two copiesof the two X chromosomes are aligned with respect to a plane 1420. In afirst cell division, each of two daughter cells 1430 and 1432 receivesone copy of each X chromosome, as indicated by arrows 414-1437. The twodaughter cells again divide to produce four germ cells 1440-1441, eachof which receives only a single X chromosome. As shown in FIG. 14C, aninternal recombination process allows portions of the sequence of one Xchromosome to be exchanged with portions of the sequence of the other Xchromosome. This process can occur between either pair of chromosomesaligned with respect to the plane 1420. Essentially, a double-strandbreak occurs at the same position within one copy of the first Xchromosome 1446 and one copy of the second X chromosome 1448, and asshown in FIG. 14C, the right-hand portions of the two broken chromosomesare exchanged and the double-stranded break is repaired to produceresulting genes that include portions of both original genes in thefirst and second X chromosomes. Such crossover events may occurrepeatedly within a single gene, allowing the genetic information withingenes to be shuffled, or recombined, during meiosis. Unfortunately,because the L and M genes are nearly identical in sequence, thealignment or registering, of each pair of chromosomes across the plane,during meiosis, may be shifted, so that, as shown in FIG. 14D, the Lgene 1460 of one chromosome ends up aligned with the M gene 1462 of theother chromosome. Crossover events can then lead to incorporation of oneor more portions of the L gene 1464 within the M gene 1466, and anadditional, redundant M gene 1468 in one product of the crossover eventand portions of the M gene 1470 in the L gene 1472, along with completedeletion of the M gene, in another product 1474 of the crossover event.As illustrated in FIG. 15, where a double-stranded chromosome isrepresented by a single entity 1480, repeated misaligned recombinationevents can lead to a large variety of different, chimeric L-gene andL-gene variants, each of which includes multiple regions onceexclusively located in either the L or M gene. In females, with two Xchromosomes, the effects of L-gene and M-gene hypervariability areameliorated by X-chromosome redundancy. However, in males, with only asingle X chromosome, the effects of L and M gene hypervariability areprofound. Fully 12 percent of human males are colorblind.

FIG. 16 illustrates the effects of genetic variation in opsin genes onthe absorbance characteristics of the opsin photoreceptor protein. Graph1602 shows an absorption curve for a normal, primordial opsinphotoreceptor protein. Graph 1604 shows the absorption curve for avariant opsin photoreceptor protein. Mutations or variations in theamino-acid sequence of an opsin photoreceptor protein can affect theabsorbance curve in various different ways. For example, the wavelengthof maximum absorbance may be shifted 1606 and the form of the curve 1608may be altered with respect to the normal curve, in many cases, thelevel of maximum absorbance may be significantly decreased 1610 withrespect to the normal level of maximum absorbance. As discussed further,below, applying filters to light prior to entry into the eye can be usedto adjust the effective absorbance spectrum of variant opsinphotoreceptor proteins with respect to normal or different variant opsinphotoreceptor proteins in order to restore the relative displacementsand magnitudes of maximum absorption observed in normal opsinphotoreceptor proteins.

FIG. 17 illustrates the effects on average spatial frequency of imagesinput to the retina produced by certain types ofopsin-photoreceptor-protein variants. As shown in FIG. 5, in graphs 511and 512, the absorbance characteristics of the M and L opsinphotoreceptor proteins are similar, with the exception that thewavelength of maximum absorption diners by 30 nanometers between the twotypes of opsin photoreceptor proteins. However, in the case of amutation to either M or L genes that produces a mutant opsinphotoreceptor protein with significantly less maximum absorbance, adiffuse image that produces low spatial frequency when input to a retinacontaining normal L and M photoreceptors produces, in a retinacontaining for example, a normal L and low-absorbing variant M opsinphotoreceptor proteins, relatively high spatial frequency. FIG. 17 usesthe same illustration conventions as used in FIG. 6. However, unlike inFIG. 6, where the M and L photoreceptor neurons have similar maximumabsorption at their respective wavelengths of maximum absorption, in thecase of FIG. 17, the M photoreceptor protein is a variant that exhibitsa significantly smaller maximum absorption at the wavelength of maximumabsorbance. In this case, a diffuse incident light, in which red andgreen wavelengths occur with relatively similar intensities and whichwould produce low spatial frequency on a normal retina, instead producesrelatively high spatial frequency due to disparity in maximum absorbanceof the variant M photoreceptor proteins and normal L photoreceptorproteins. In FIG. 17, edges, such as edge 1702, have been drawn betweenthe M and L photoreceptor neurons. Whereas, in the normal retina, shownin FIG. 6, no edges would be produced by the diffuse light, to theretina containing mutant M photoreceptor protein, edges occur throughoutthe retina, between adjacent L and M photoreceptor neurons. Thus, theperceived spatial frequency by the retina containing variant,low-absorbing M photoreceptor neurons is much higher than would beperceived in a normal retina by a diffuse or blurred image. Therefore,in many individuals with low-absorbing variant photoreceptor proteinsthe decrease in spatial frequency past the spatial frequency thresholdthat results in inhibiting further eye growth, in normal individuals, asdiscussed above with reference to FIG. 9A, does not occur, and insteadthe eye remains in state 934, shown in FIG. 9B, in which the eyecontinues to respond to an eye-lengthening signal despite the fact thataxial length of the eye has exceeded the axial length for properdevelopment and focus.

FIG. 18 illustrates the predictability of the degree of myopia inindividuals with various types of mutant opsin photoreceptor proteins,according to one embodiment of the present invention. An observed degreeof myopia, plotted with respect to the horizontal axis 1802, is shown tobe strongly correlated with degrees of myopia predicted for the variousphotoreceptor-protein mutations, or haplotypes, plotted with respect tothe vertical axis 1804. Predictions can be made on the detailedstructure of photoreceptor proteins provided by x-ray crystallography,molecular-dynamics simulations, and results from application ofadditional computational and physical techniques that provide aquantitative, molecular basis for understanding the effects, on lightabsorption, by changes in the sequence and conformation of photoreceptorproteins. Sequencing the L and M opsin genes for a patient can thereforereveal variant-photoreceptor-induced myopia or nascentvariant-photoreceptor-induced myopia, and can further reveal the degreeof myopia expected for the variant-photoreceptor-induced myopia, whichcan, in turn, inform the degree of artificial blurring that needs to beapplied to the patient at each point during application of artificialblurring.

In individuals with eye-length-related disorders wising from variantphotoreceptor-protein genes, the use of glasses, or contact lenses, thatincorporate wavelength filters can restore the relative absorptioncharacteristics of the different types of photoreceptor proteins, andthus remove the variant-photoreceptor-protein-induced increase inspatial frequency and thus force a transition from uninhibited eyelengthening, represented by state 934 in FIG. 9C, to state 940, in whichthe eye responds to a lack of positive eye-lengthening signal or anegative feedback signal. FIGS. 19A-B illustrate characteristics of thefilters employed in the therapeutic devices used to treatvariant-photoreceptor-protein-induced myopia as well as myopia inducedby other, or combinations of other, environmental behavioral, or geneticfactors, according to certain embodiments of the present invention. Asshown in FIG. 19A, in the case that the M photoreceptor protein variantabsorbs light less efficiently than a normal M photoreceptor protein, afilter that preferentially transmits wavelengths in region 1904 willtend to boost M-photoreceptor-protein absorption greater thanL-photoreceptor-gene absorption, and thus restore the balance betweenphotoreception by the normal L photoreceptor protein and photoreceptionby the variant M photoreceptor protein. By contrast as shown in FIG.19B, when the L photoreceptor gene is defective, and absorbs less thannormal L photoreceptor protein, filters that preferentially pass lightin the wavelength range 1906 will boost absorption by the variant Lphotoreceptor protein more than absorption by the M photoreceptorprotein, thus restoring the balance of absorption between the twodifferent types of photoreceptor proteins.

FIGS. 20A-I illustrate, using exemplary ƒ(x) and g(x) functions, theconvolution operation ƒ(x)·g(x), of two functions ƒ(x) and g(x). Theconvolution operation is defined as;

f(x) * g(x)∫_(−∞)^(∞)f(α)g(x − α) α

where a is a dummy variable of integration.

FIGS. 20A and 20B show two step functions ƒ(a) and g(a). The functionƒ(a) has a value of 1 for values of a between 0 and 1 and has a value of0 outside that range. Similarly, the function g(a) has a value of ½ forvalues of a between 0 and 1 and has a value of 0 outside that range.FIG. 20C shows the function g(−a), which is the mirror image of thefunction g(a) through the vertical axis. FIG. 20D shows the functiong(x−a) for a particular x 2002 plotted with respect to the a axis. FIGS.20E-H illustrate the product ƒ(a)g(x−a) for a number of different valuesof x. Finally, FIG. 20I illustrates the convolution of functions ƒ(x)and g(x) according to the above expression. The function ƒ(x)*g(x) has avalue, at each value of x, equal to the area of overlap between the ƒ(a)and g(x−a) functions, as shown by the shaded areas 2006-2008 in FIGS.20F-H. In other words, convolution can be thought of as generating themirror image of the function g(x) and translating it from −∞ to ∞ alongthe a axis with respect to the ƒ(a) function, at each point computingthe value of the convolution as the area of overlap between ƒ(a) andg(x−a). The area under the ƒ(x)*g(x) curve, for a given function g(x) ismaximized when the function ƒ(x) is equal to, or contains, the functiong(x). Thus, the integral of the convolution of two functions from −∞ to∞ provides a measure of the overlap between the two functions:

overlap  of  f(x)  and  g(x)  is  related  to  ∫_(−∞)^(∞)f(x)* g(x)

Thus, using either the above integral or summation over discreteintervals, convolution of the absorbance spectrum of a filter and theabsorbance spectrum of a photoreceptor protein provides a measure of theoverlap of the absorbance filter and photoreceptor protein. Thus, anM-boosting metric can be computed from a given filter, with absorbancespectrum T(λ), by the ratio:

$M = \frac{{\int_{\lambda = {- \infty}}^{\infty}{{T(\lambda)}*{A_{M}(\lambda)}}}\ }{{\int_{\lambda = {- \infty}}^{\infty}{{T(\lambda)}*{A_{i}(\lambda)}}}\ }$

where A_(M) (λ) and A_(L) (λ) are the absorbance spectra of M opsin andL

-   -   opsin, respectively.        Filters with M-boosting metrics significantly greater than 1 may        be useful in correcting myopia in individuals with low-absorbing        M-variant photoreceptor proteins, while filters with M-boosting        metrics significantly below 1 may be useful in treating myopia        in individuals with low-absorbing variant L-photoreceptor        proteins. The M-boosting metric may be computed using summations        over discrete wavelengths within the visible spectrum, rather        than by integration. In general, various closed-form or numeric        expressions for the absorption spectra of the L and M opsins may        be used. The convolution operation becomes a multiplication for        Fourier-transformed functions ƒ(x) and g(x), F(x) and G(x),        respectively. It is generally more efficient to        Fourier-transform ƒ(x) and g(x), compute the product of F(x) and        G(x), and the apply an inverse Fourier transform to F(x)G(x) in        order to produce ƒ(x)·g(x).

Therapeutic devices that represent embodiments of the present inventionmay include filters and well as blur-inducing coatings, inclusions,bumps, or depressions. The filter-based approach may be applied to avariety of different types of variants, including variants that showshifting of wavelength of maximum absorption, decreased absorption, andcomplex alteration of the absorbance curve, in order to restore thenormal balance between the absorption characteristics of various typesof opsin photoreceptor proteins. Many different techniques and materialscan be employed to produce lens materials with particular, complexabsorption characteristics.

Although the present invention has been described in terms of particularembodiments, it is not intended that the invention be limited to theseembodiments. Modifications will be apparent to those skilled in the art.For example therapeutic inventions, in which artificial focusing, ratherthan artificial blurring, is employed may correct eye-length-relateddisorders in which the axial length of the eye is shorter than a normallength, and the eye has failed to grow in response to high spatialfrequency. Blur-inducing glasses and contact lenses andwavelength-dependent filtering glasses and contact lenses are but twoexamples of a variety of different methods for inducing artificialblurriness in order to halt eye lengthening in myopic or myopia-disposedindividuals, methods used to identity individuals with eye-lengtheningdisorders or individuals disposed to eye-lengthening-related disordersmay include currently available vision-evaluation techniques used byophthalmologists and optometrists, instrumentation for correctlymeasuring the axial length of the eye, genetic techniques fordetermining the precise opsin-photoreceptor-protein variance, oramino-acid sequences, in patients, and other techniques. It should benoted that all of the various therapeutic devices that can be devised,according to the present invention, may find useful application in eachof the various types of eye-length-related disorders, whatever theirunderlying environmental, behavioral, or genetic causes. Wavelengthfilters incorporated into lenses, for example, may provide benefit toindividuals in which myopia is induced by excessive reading, and notonly to those individuals with low-absorbing photoreceptor-proteinvariants. While therapeutic devices worn by individuals are discussed,above, any therapy that induces artificial blurring, as also discussedabove, that results in a transition of the eye from a state in which theeye is non-responsive to a negative feedback signal or continues togenerate and/or respond to a positive eye-growth sign to a state inwhich eye lengthening is halted is a potential therapeutic embodiment ofthe present invention. For example, drugs, including muscarinic receptoragonists, which would cause the ciliary body to contract and thereforeadjust the focus of the eye to a shorter focal length at which distanceobjects fail to completely focus, are candidate drug therapies forintroducing artificial blurring according to the present invention. Mostcurrently-available muscarinic receptor agonists also cause the pupil tocontract, changing the depth of field. A particularly useful drug fortherapeutic application, according to embodiments of the presentinvention, would not cause the pupil to contract or dilate. When thepupil remains at normal size for ambient lighting conditions, the depthof field remains sufficiently small, so that a relatively small amountof the visual field is well focused.

The foregoing description, for purposes of explanation, used specificnomenclature to provide a thorough understanding of the invention.However, it will be apparent to one skilled in the art that the specificdetails are not required in order to practice the invention. Theforegoing descriptions of specific embodiments of the present inventionare presented for purpose of illustration and description. They are notintended to be exhaustive or to limit the invention to the precise formsdisclosed. Many modifications and variations are possible in view of theabove teachings. The embodiments are shown and described in order tobest explain the principles of the invention and its practicalapplications, to thereby enable others skilled in the art to bestutilize the invention and various embodiments with various modificationsas are suited to the particular use contemplated. It is intended thatthe scope of the invention be defined by the following claims and theirequivalents:

1. A therapeutic treatment method for preventing, ameliorating, orreversing eye-length-related disorders, the therapeutic treatment methodcomprising: identifying, in a patient, an eye-length-related disorder;and inducing artificial blurring of the patient's vision in order todecrease an average spatial frequency of images input to the retina ofthe eye past a threshold spatial frequency to inhibit furtherlengthening of the patient's eye.
 2. The method of claim 1 furtherincluding: determining a degree to which the axial length of thepatient's eye exceeds an axial length that provides a normal focallength for the relaxed eye; and inducing artificial blurring of thepatient's vision commensurate with the determined degree to which theaxial length of the patient's eye exceeds the axial length that providesthe normal focal length for the relaxed eye in order to decrease anaverage spatial frequency of images input to the retina of the eye pasta threshold spatial frequency to inhibit further lengthening of thepatient's eye.
 3. The method of claim 1 further including: determining atype of eye-length-related disorder in the patient; and inducingartificial blurring of the patient's vision commensurate with thedetermined type of eye-length-related disorder in order to decrease anaverage spatial frequency of images input to the retina of the eye pasta threshold spatial frequency to inhibit further lengthening of thepatient's eye.
 4. The method of claim 3 wherein determining the type ofeye-length-related disorder in the patient further includes one or moreof: conducting direct eye-axial-length measurement; conducting standardvision-acuity tests; and sequencing the patient's opsin genes todetermine the types of opsin variants that occur within the patient. 5.The method of claim 1 wherein inducing artificial blurring of thepatient's vision in order to decrease the average spatial frequency ofimages input to the retina of the eye past a threshold spatial frequencyto inhibit further lengthening of the patient's eye further includes:providing the patient with a therapeutic device selected fromblur-inducing glasses; blur-inducing contact lenses; and blur-inducingglasses that incorporate wavelength-dependent filters.
 6. The method ofclaim 5 wherein the blur-inducing glasses induce blurring by one or moreof: small bumps or depressions in one or both surfaces of the lenses;inclusions within the lenses of a material different from the lensmaterial; incorporation of higher-level aberrations in the lenses,including higher-level aberrations that more greatly affect peripheralvision; providing progressive negative corrections in one or both lensesfrom the top of the lenses to the bottom of the lenses, coatings orfilms applied to one or both surfaces of the lenses.
 7. The method ofclaim 5 wherein the blur-inducing contact lenses induce blurring by oneor more of: inclusions within the lenses of a material different fromthe lens material; incorporation of higher-level aberrations in thelenses, including higher-level aberrations that more greatly affectperipheral vision; providing progressive negative corrections in one orboth lenses from the center of the lens to the bottom of the lenses;coatings or films applied to one or both surfaces of the lenses.
 8. Themethod of claim 1 wherein inducing artificial bluffing of the patient'svision in order to decrease the average spatial frequency of imagesinput to the retina of the eye past a threshold spatial frequency toinhibit further lengthening of the patient's eye further includes:treating the patient with a therapeutic drug that shortens the focallength of the eye without causing unnatural dilation or contraction ofthe pupil.
 9. The method of claim 9 wherein the drug is amuscarinic-receptor agonist.
 10. A therapeutic treatment method forpreventing, ameliorating, or reversing eye-length-related disorders, thetherapeutic treatment method comprising: identifying, in a patient, atype of eye-length-related disorder related to variant opsinphotoreceptor proteins within the patient; and restoring a normalbalance between the absorption characteristics of the different opsinphotoreceptor proteins within the patient in order to decrease anaverage spatial frequency of images input to the retina of the eye pasta threshold spatial frequency to inhibit further lengthening of thepatient's eye.
 11. The method of claim 10 wherein determining the typeof eye-length-related disorder in the patient further includes one ormore of: conducting direct eye-axial-length measurement; conductingstandard vision-acuity tests; and sequencing the patient's opsin genesto determine the types of opsin variants that occur within the patient.12. The method of claim 10 wherein restoring a normal balance betweenthe absorption characteristics of the different opsin photoreceptorproteins within the patient in order to decrease an average spatialfrequency of images input to the retina of the eye past a thresholdspatial frequency to inhibit further lengthening of the patient's eyefurther includes: providing the patient with a therapeutic deviceselected from glasses incorporating wavelength-dependent filters;contact lenses incorporating wavelength-dependent filters; blur-inducingglasses that incorporate wavelength-dependent filters; and blur-inducingcontact lenses incorporating wavelength-dependent filters.
 13. Themethod of claim 12 wherein the blur-inducing glasses induce blurring byone or more of: small bumps or depressions in one or both surfaces ofthe lenses; inclusions within the lenses of a material different fromthe lens material; incorporation of higher-level aberrations in thelenses, including higher-level aberrations that more greatly affectperipheral vision; providing progressive negative corrections in one orboth lenses from the top of the lenses to the bottom of the lenses;coatings or films applied to one or both surfaces of the lenses.
 14. Themethod of claim 12 wherein the blur-inducing contact lenses induceblurring by one or more of: inclusions within the lenses of a materialdifferent from the lens material; incorporation of higher-levelaberrations in the lenses, including higher-level aberrations that moregreatly affect peripheral vision; providing progressive negativecorrections in one or both lenses from the center of the lens to thebottom of the lenses; coatings or films applied to one or both surfacesof the lenses.
 15. The method of claim 12 wherein thewavelength-dependent filters have absorption characteristics that: boostabsorption by low-light-absorbing photoreceptor variants relative toother photoreceptors.
 16. The method of claim 12 wherein thewavelength-dependent filters have absorption characteristics that:decrease light absorption by photoreceptor variants relative to otherphotoreceptors.
 17. A therapeutic device for preventing, ameliorating,or reversing eye-length-related disorders, the therapeutic devicecomprising one of: blur-inducing glasses; blur-inducing contact lenses;blur-inducing glasses that incorporate wavelength-dependent filters;blur-inducing contact lenses that incorporate wavelength-dependentfilters; glasses that incorporate wavelength-dependent filters; andcontact lenses that incorporate wavelength-dependent filters;
 18. Thetherapeutic device of claim 17 wherein blur-inducing glasses induceblurring by one or more of: small bumps or depressions in one or bothsurfaces of the lenses; inclusions within the lenses of a materialdifferent from the lens material; incorporation of higher-levelaberrations in the lenses, including higher-level aberrations that moregreatly affect peripheral vision; providing progressive negativecorrections in one or both lenses from the top of the lenses to thebottom of the lenses; coatings or films applied to one or both surfacesof the lenses.
 19. The therapeutic device of claim 18 wherein the bumps,depressions, inclusions, coatings, or films provide increasingblur-induction from a central, non-blur-inducing region outward.
 20. Thetherapeutic device of claim 19 wherein one lens of the therapeuticdevice has a central, non-blur-inducing region and the other lens has acentral, minimal-blur inducing region.
 21. The therapeutic device ofclaim 17 wherein blur-inducing contact lenses induce blurring by one ormore of: inclusions within the lenses of a material different from thelens material; incorporation of higher-level aberrations in the lenses,including higher-level aberrations that more greatly affect peripheralvision; providing progressive negative corrections in one or both lensesfrom the cent et of the lens to the bottom of the lenses; coatings orfilms applied to one or both surfaces of the lenses.
 22. The therapeuticdevice of claim 21 wherein the inclusions, coatings, or films provideincreasing blur-induction from a central, non-blur-inducing regionoutward.
 23. The therapeutic device of claim 21 wherein the inclusions,coatings, or films provide increasing blur-induction from a central,minimum-blur-inducing region outward.
 24. The therapeutic device ofclaim 17 wherein the wavelength-dependent filters have absorptioncharacteristics that: boost absorption by low-light-absorbingphotoreceptor variants relative to other photoreceptors.
 25. Thetherapeutic device of claim 17 wherein the wavelength-dependent filtershave absorption characteristics that: decrease light absorption byphotoreceptor variants relative to other photoreceptors.